Anaemia I Flashcards
Define anaemia.
Hb level below normal.
What are ‘normal’ Hb levels affected by?
Age
Sex
Pregnancy
Altitude
Effects of anaemia
A slightly depressed Hb level may be asymptomatic (Hb 70-100 g/L)
More severe or impaired cardiorespiratory system
- Tiredness
- Palpitations
- Short of breath
- Angina
- Cardiac failure
What determines the Hb level?
The Hb level is a balance between:
- Production of RBC in bone marrow, which needs:
- Normal blood forming cells
- Haematinics and hormones (EPO)
- Absence of inhibitors (inflammatory cytokines)
- Shortened time of RBC in circulation
- Blood loss from circulation: haemorrhage
- Shortened RBC life span: haemolysis
A change in level of Hb can either be a failure of production or increased breadown or loss.
Reticulocyte count
- Measure of recently produced RBC (1-2 days old)
- Measure of marrow erythropoietic activity.
- Increased = healthy marrow response to anaemia
- Reduced/low-normal = ?marrow (production) pathology
Haematinics
Iron studies
B12 and folate
Tests for haemolysis
Bilirubin, haptoglobin, LDH
Measure of increased RBC breakdown.
Bone marrow aspirate and trephine
Assesses marrow activity, function +/- presence of abnormal cells
Aspirate
- Cellular details
- Iron stores
Trephine
- Overall view of BM structure
- Better assessment of cellularity
- Patchy abnormalities e.g. lymphoma
Classification of anaemias
**Decreased production **(synthetic failure) vs. **increased destruction/loss **(bleeding, haemolysis…)
or
**MCV **(mean corpuscular volume of RBC)
- Microcytic = ‘too small’
- Normocytic = ‘just right’
- Macrocytic = ‘too big’
Microcytic anaemic causes
- Iron deficiency
- Anaemia of chronic disease (ACD)
- Thalassaemias/haemoglobinopathies
- Others
- Congenital sideroblastic anaemia (rare)
- Lead poisoning
Microcytic anaemia common features
Failure of adequate Hb incorporation into RBC.
Iron deficiency: lack of iron for haem.
ACD: block of iron transfer into RBC
Thalassaemia/haemoglobinopathies: problem with production of globin chain for Hb molecule.
Anaemic of chronic disease
- May be microcytic of normocytic.
- Also may be hypochromic or normochromic.
Irons stores fail to incorporate iron into RBC.
- BM resistant to EPO
- Inadequate production of EPO in response to anaemia
Not helped by iron therapy (can have mixed Fe deficiency and ACD).
Treat underlying cause + EPO *may *help.
Iron findings
- Transferrin low: production inhibited in inflammation, acute phase response.
- Serum ferritin high: increased body iron stores, increased in inflammation (acute phase)
- BM iron increased: increased iron in macrophages.
Causes
- infection
- Inflammatory disorders: rheumatoid, SLE etc
- Malignancy
Iron studies in iron deficiency
Never look at serum iron.
Ferritin reduced = iron deficiency
_Ferritin _normal/low-normal = ?iron defiency
- Acute phase response
- Look at transferrin saturation (if reduced - iron deficiency is likely)
Causes of iron deficiency
Blood loss
- Iron deficiency in an adult Australian is bowel cancer until proven otherwise
Dietary
- Vegetarians/vegans
- Infants (cow milk protein/lactose intolerance), adolescents
- Pregnancy (increased requirement)
- Menorrhagia/increased requirement
- Elderly
Malabsorption
- Coeliac disease
- Crohn’s
Causes of macrocytic anaemia
Magaloblastic
- B12, folate, medication (folate depletion - e.g. MTX), BM disorders.
Non-megaloblastic
- Increased reticulocyte count e.g. acute bleed or haemolysis
- Normal reticulocyte count
- Liver disease/alcohol
- Hypothyroidism
- Bone marrow disorders
Spurious
- E.g. Myeloma
Blood film findings in megaloblasic anaemia
- Single/pancytopenia
- Macrocytosis +/- oval macrocytes
- Hypersegmented neutrophils
Vitamin B12 deficiency causes
Dietary
- Rarely except strict vegans
Malabsorption
- Lack of instrinsic factor
- Pernicious anaemia
- Gastrectomy
- Intrinsic factor present
- Terminal Ileal disease (IBD) or resection
Metabolic causes (rare)
Effects of B12 deficiency
Dividing cells and neurological
- Megaloblastic anaemia
- Gastrointestinal effects
- Neurological
- Peripheral neuropathy
- Subacute combined degeneration of cord
- Other (delirium screen)
Haemoglobinopathies
Thalassaemia
Haemoglobin variants
Thalassaemia
Decreased rate of production of one of the globin chains, causing an ‘imbalance’ and therefore red cell changes.
Alpha thalassaemia: decreased production of alpha globin chains
Beta thalassaemia: decreased production of beta globin chains
Haemoglobin variants
Production of Hb with an abnormal globin chain e.g. HbS
Most common is sickle cell disease
Amino acid substitution in globin chain.
Alpha thalassaemia
Number of alpha genes deleted
- One or two: alpha thal trait (asymptomatic)
- Three: Hb H disease (mild to moderate disease)
- Four: hydrops fetalis (incompatible with life)
Homozygous alpha thalassaemia
Hydrops fetalis
4 alpha globin genes deleted.
Cannot make HbF, HbA or HbA2
Severe anaemia
Fatal pre-term
Beta thalassaemias
Decreased production of beta globin chain
Homozygous: severe disease
Heterozygous: asympotmatic, microcytic RBC
Homozygous beta thalassaemia
Marked decrease in HbA (decreased beta globin chains, excess alpha globin chains).
Symptoms from age 3-6 months (HbF)
Severe anaemia plus:
- Erythroid hyperplasia ++ and bony malformations
- Hepatosplenomegaly
- Iron overload
- Cardiomyopathy, endocrine disorders etc.
Transfusion dependent for life
Haemoglobin E
Substitution one amino acid in beta globin chain.
Common in South East Asia.
HbE homozygous and heterozygous
- Asymptomatic
- Low MCV and blood film changes only
Double heterozygote HbE + beta thal
- Severe disease (like beta thal major)
Haemoglobin S
Substitution one amino acid in beta globin chain.
HbS less soluble and precipitates in hypoxia (sickling)
_Heterozygous HbS (_sickle cell trait)
- Asymptomatic with normal FBC and film
Homozygous HbS (sickle cell anaemia)
- Severe disease
- Anaemia, sickle cell crises with pain and vascular occlusion by sickling cells
Bone marrow failure syndromes
Aplasia: decrease in haemopoietic cells
Dysplasia: BM cells abnormal
Bone marrow infiltration: BM replacement
Anaemia due to aplasia
General BM failure
- Aplastic anaemia
- Pancytopenia - low Hb, WBC and platelets
Specific to RBC
- Pure red cell aplasia - parvovirus, autoimmune
Bone marrow dysplasia
Bone marro wnromal or increased cellularity but cells look abnormal and are dysfunction.
Primary myelodysplastic syndromes
- Acquired bone marrow genetic change
- Often high MCV and low WBC and/or platelets
Secondary
- Medication, pyridoxine deficiency, heavy metal poisoning
Erythropoiesis in a dysplastic BM
Disturbed erythropoiesis
- Increased RBC precursors
- Abnormal morphology
- Decreased RBC production (ineffective)
Haemolytic anaemia
Anaemia due to shortened RBC life span.
Two sites of haemolysis
- Extravascular (in reticuloendothelial cells)
- Intravascular
Evidence of haemolysis
- Morphological evidence of red cell damage
- Spherocytes
- RBC fragmentation
- Biochemical evidence of red cell breakdown
- Increased *unconjugated bilirubin *(jaundiced)
- Decreased haptoglobin (rapid test)
- Increased LDH (non-specific)
- Increased rate of RBC production
- Increased polychromasia (bluish RBC)
- Increased reticulocyte count
Causes of haemolytic anaemia
- Congenital
- Acquired
also classified as
-
Extrinsic (change in blood or blood vessels)
- Autoimmune haemolytic anaemia
- Drugs
- DIC, mechanical valve
-
RBC membrane
- __Hereditary spherocytosis
-
RBC cytoplasm
- G6PD deficiency
Investigation of haemolysis
-
Is this patient haemolysing?
- FBC and blood film
- Reticulcyte count
- Bilirubin, urobilinogen
- Haptoglobin
- LDH
-
What is the cause? Is it immune mediated (AIHA)?
- Clinical
- RBC morphology from film
- Spherocytes
- Fragments
- Specific features e.g. sickle cell
- DAT (direct antiglobin test)
- Other special tests
Direct antiglobin test
Detects antibody on RBC
Add anti-human Ig to RBC
If antibody on RBC then added anti human Ig cross links RBC causing agglutination (DAT positive)
Autoimmune hamolytic anaemia
Autoantibodies to own RBC
Increased haemolysis with spherocytes and polychromasia
DAT positive.
